Improved clinical outcome following liver transplant in patients with ethylmalonic encephalopathy

Allison Tam, Noura Salem AlDhaheri, Krupa Mysore, Mary Elizabeth Tessier, John Goss, Luis A. Fernandez, Anthony M. D'Alessandro, Jessica Scott Schwoerer, Gregory M. Rice, Sarah H. Elsea, Fernando Scaglia

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


Ethylmalonic encephalopathy (EE) is a rapidly progressive autosomal recessive mitochondrial disease caused by biallelic pathogenic variants in the ETHE1 gene that encodes the mitochondrial sulfur dioxygenase. It is characterized by neurodevelopmental delay and regression, pyramidal and extrapyramidal signs, recurrent petechiae, chronic diarrhea, and orthostatic acrocyanosis. Laboratory findings include elevated serum levels of lactate and C4-C5 acylcarnitines, and elevated urinary excretion of ethylmalonic acid and C4-C6 acylglycines, notably isobutyrylglycine and 2-methylbutyrylglycine. These findings are attributed to deficiency of the mitochondrial sulfur dioxygenase resulting in toxic accumulation of hydrogen sulfide metabolites in vascular endothelium and mucosal cells of the large intestine. Medical management has thus far been directed toward decreasing the accumulation of hydrogen sulfide metabolites using a combination of metronidazole and N-acetylcysteine. More recently, orthotopic liver transplant (OLT) has been reported as a new therapeutic option for EE. Here, we report two additional cases of EE who achieved psychomotor developmental improvement after 7- and 22-months following OLT. The second case serves as the longest developmental outcome follow-up reported, thus far, following OLT for EE. This report provides additional evidence to validate OLT as a promising therapeutic approach for what was considered to be a fatal disease.

Original languageEnglish
Pages (from-to)1015-1019
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Issue number6
Publication statusPublished - Jun 2019


  • ETHE1
  • ethylmalonic encephalopathy
  • hydrogen sulfide toxicity
  • mitochondrial sulfur dioxygenase
  • orthotopic liver transplant

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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